Pathology of testicular tumors

testicular tumors have high rates in Scandinavian countries and low prevalence in blacks compared to whites

1. PATHOLOGY OF TESTICULAR TUMORS PATHOLOGY OF TESTICULAR TUMORS By Nebiyou S. R-I Moderator- Dr.Ashebir (consultant surgeon ) Jimma university,2017

2. Outline Embryogenesis & gross anatomy Epidemiology and Etiology Carcinoma in situ of Testis Testicular Neoplasms Classification Discussion of Pathologic classes Natural history & patterns of spread Clinical features & Staging Treatment overview Summary

3. Testes: Embryogenesis Descend from dorsal abdominal wall to deep inguinal ring during 9 th to 12 th fetal weeks Processus vaginalis, out pouching of peritoneum ,the later tunica vaginalis , and gubernaculum guide it Final descent before or shortly after birth

4. Testes : Anatomy Suspended by spermatic cord in the scrotum Produce spermatozoa (Seminiferous tubules) and hormones (testosterone) Tunica vaginalis: visceral and parietal layers Outer cover, tunica albuginea, beneath the vaginalis Testicular arteries arise from abdominal aorta and come through spermatic cord.

5. Testes: Anatomy cont’d… Testicular veins form pampiniform venous plexus, thermoregulatory system of the testes . Left TV drains to Left renal vein and the Right one to IVC. Lymphatic drainage is to Lumbar and Pre-aortic lymph nodes. Nerve supply is Vagal for parasympathetic and afferent; sympathetics from T7

6. Epidemiology High rates in S candinevia,German & Switzerland and low in Africa and Asia Ethiopia? More common in whites than blacks –five fold Higher incidence in relatives, ? Recessive inheritance More common on the Rt side 2-3% bilateral

7. Etiology Multifactorial Genetic (i12p) V s environmental Four well established risk factors Cryptorchidism- F amily history of testicular cancer- RR higher in brothers than sons P ersonal history of testicular cancer- 12 X risk I ntratubular germ cell neoplasia- 50% in 5 yrs ,70% in 7 yrs for GCT

8. Cont’d… Congenital Cryptorchidism = 4 -6X In 7-10 % of patients Risk rate=2-3X if orchidopexy done before puberty T esticular dysgenesis syndrome Acquired Trauma? Hormones Inutero DES exposure Atrophy Environmental

9. Carcinoma In Situ (CIS)/ITGCN Preinvasive precursor of all testicular GCTs except spermatocytic seminoma Incidence 0.8%(Denmark) Two models- arrested gonocyte Vs aberrant chromatid exchange Risk factors include: testicular ca hx , EGCT, cryptorchidism, somatosexual ambiguity and inferitility Characterized by Seminiferous tubules with sertoli cells and malignant germ cells limited to the basement membrane

10. Pathologic classification

11. Classification Cont’d…

12. Classification Cont’d…

13. Classification Cont’d…

14. Classification c ont’d…

15. Pathologic Classes General pathologic classification: Germ Cell Tumors Non-Germinal Tumors Germ Cell Tumors account for 95% of all testicular tumors Non-Germinal Tumors include Stromal and Sex-cord tumors

16. Germ Cell Tumors (GCT) They are composed of five basic cell types: Seminoma Embryonal Cell Carcinoma Yolk Sac Tumor Teratoma Choriocarcinoma About 50-60% of GCTs are mixed Non- Seminomatous GCTs

17. GCT cont’d… Seminoma Make 50% of GCTs Peak incidence in 30s Mainly thru lymphatic route 3 subtypes Classic Anaplastic Spermatocytic

18. GCT cont’d… Classic /Typical Seminoma 82-85% of all seminomas , men in their 30s Grossly homogenous, lobulated, gray-white mass devoid of hemorrhage or necrosis, intact tunica albuginea Histology islands or sheets of large cells with clear cytoplasm and densely staining nucleoli, lymphocytic infiltrate 10-15% are β - hCG producing ( presence of syncytiotrophoblasts )

19. GCT cont’d…

20. GCT cont’d… Anaplastic Seminoma 5-10% of seminomas Same age distribution as classic seminoma features suggestive include More mitotic activity More local invasion rate & metastatic spread Higher incidence of β - hCG production

21. GCT cont’d… Spermatocytic Seminoma 2-12% of all seminomas 50% occur in men in their 50s Low metastatic potential Favorable prognosis

22. NSGCTs Embryonal Carcinoma Peak incidence 3 rd & 4 th decades More aggressive than seminomas Grossly variegated, grayish whit, fleshy tumor with necrosis or hemorrhage and poorly defined capsule. Histologically malignant epitheloid cells in glands or tubules Highly malignant , hence pleomorphism and high mitotic figures are common most undifferentiated cell type of NSGCT( totipotential ) May be positive for β - hCG & AFP

23. NSGCTs cont’d…

24. NSGCTs cont’d… Teratoma a neoplasm exhibiting simultaneous differentiation along endodermal, mesodermal and ectodermal lines. Occur at any age; tend to be mature in children and act as benign but in post-pubertal males they are malignant whether mature or immature. Mature elements resemble derivatives of the 3 germ layers Immature elements are undifferentiated and resemble primitive tissues.

25. NSGCTs cont’d… Grossly large lobulated and non- homogenous . Cut surface consists of cysts with solid tissues in between, cartilage and bone. Histologically different types of specialized cells.

26. NSGCTs cont’d…

27. NSGCTs cont’d… Figure 18-9 Teratoma. Testicular teratomas contain mature cells from endodermal, mesodermal, and ectodermal lines. Pictured here are four different fields from the same tumor containing neural (ectodermal) (A), glandular (endodermal) (B), cartilaginous (mesodermal) (C), and squamous epithelial (D) elements.

28. NSGCTs cont’d… Yolk sac / Endodermal Sinus Tumor Seen commonly in infants and young kids Grossly variegated gray white like embryonal cell carcinoma Microscopically – 3 patterns: Microcystic , Endodermal sinus and Solid.

29. NSGCTs cont’d…

30. NSGCTs cont’d… Choriocarcinoma Highly malignant, composed of both cyto and syncytiotrophoblastic cells. Usually mixed with other types. Primary tumor is usually small but may present with distant metastasis(extensive LVI) Grossly present with central hemorrhage with viable grayish whit tumor at periphery Histologically polygonal uniform cytotrophoblastic cells in sheets and cords mixed with syncytiotrophoblasts May bleed like GTD-catastrophic if in lung&brain Positive for β - hCG

31. NSGCTs cont’d…

32. Non-Germinal Tumors Sex cord- Stromal Tumors- 90% are benign Leydig / Interstitial Cell Tumors 2% of all testicular tumors; may occur 20-60 yrs. Produce androgens and other steroids Masculinising -sexual precocity 10% metastatic or invade Sertoli Cell Tumors / Androblastoma uncommon, most benign May elaborate estrogens or androgens but in small amounts Feminising-gynecomastia,loss of libido 10% invade or metastatasis

33. Non-Germinal Tumors cont’d… Testicular lymphoma 5% of all testicular tumors Most common in people above 60 yrs. Most are diffuse, large B cell NHL which disseminates widely Poor prognosis

34. Natural history and Patterns of spread ITGCN after malignant transformation involves the testicular parenchyma Local - involvement of epididymis or spermatic cord is hindered by tunica vaginalis ; hence, hematogenous or lymphatic spread may occur first(RPLNs) Lymphatic-main route for all except choriocarcinoma Hematogenous spread to lung, bones or liver mainly choriocarcinoma

35. Clinical Features & Staging Symptoms Nodule or painless swelling, dull ache (30-40%) or heavy sensation Acute pain (10%)-hemorrhage into tumor Metastatic symptoms(10%)- neck mass, respiratory symptoms, GI symptoms, Lumbar back pain, bone pain, CNS manifestations Gynecomastia (5%)

36. Clinical Features cont’d… Signs Mass in the testis Do bimanual examination Look for examination NB: Any patient with a solid, firm, intratesticular mass, Testicular Ca must be the diagnosis UPO

37. Clinical Staging Clinical staging is based on pathologic analysis of primary tumor and imaging studies of chest and retroperitoneum Investigation CXR ( PA,lateral ) CT(abdominopelvic ) Tumor markers AFP β - hCG LDH

38. Clinical staging C ont’d …

39. Risk classification and prognosis

40. Treatment overview Testicular cancer has become one of the most curable solid neoplasms and serves as a paradigm for the multimodal treatment of malignancies . The broad distinction between seminomas and nonseminomas has been particularly important in determining management strategies for retroperitoneal lymph node metastasis. Modalities of treatment include radical/ inguinal orchiectomy + RPLND, radiation and chemotherapy

41. Summary Most common tumors in men aged between 15-35 yrs . Broadly classified into: germ cell (95%) and Non-germinal tumors Two classes of GCTs: Seminomatous and Non- seminomatous . Testicular self examination Staging is based on TNM and serum markers Most curable solid neoplasm with multimodal treatment-model for curable neoplasm

42. REFERENCES

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